
==== Front
J Anesth
J Anesth
Journal of Anesthesia
0913-8668
1438-8359
Springer Nature Singapore Singapore

38967786
3368
10.1007/s00540-024-03368-8
Original Article
Real-time analgesic efficacy and factors determining drug requirements of combined spinal-epidural analgesia for labor: a prospective cohort study
Wu Shuzhen 1
Lu Yaxin 2
Zhang Zijing 1
Zhong Linjia 1
Dai Hongfei 1
Fang Changping 1
Huang Minli 1
Liu Zifeng 2
http://orcid.org/0000-0003-4995-1790
Wu Lingling 2806381451@qq.com

1
1 https://ror.org/0064kty71 grid.12981.33 0000 0001 2360 039X The Department of Obstetrics and Gynecology, The Third Affiliated Hospital Sun Yat-Sen University, No. 600 Tianhe Road, Tianhe District Guangzhou, Guangdong, China
2 https://ror.org/0064kty71 grid.12981.33 0000 0001 2360 039X Big Data and Artificial Intelligence Center, The Third Affiliated Hospital Sun Yat-Sen University, Guangzhou, Guangdong, 510630 China
5 7 2024
5 7 2024
2024
38 5 656665
9 5 2023
20 6 2024
© The Author(s) 2024
2024
https://creativecommons.org/licenses/by/4.0/ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
Purpose

Combined spinal-epidural analgesia (CSEA) is effective but not sufficient for labor pain. This study was conducted to assess the real-time analgesic efficacy, side effects of anesthetic drug dosage, and maternal satisfaction in labor to provide reference for the optimization of labor analgesia.

Methods

This was a prospective, cohort, single-center study that included 3020 women who received CSEA for labor analgesia. The visual analogue scale (VAS) for labor pain, real-time anesthetic drug dosage, side effects, adverse labor outcomes, factors influencing average drug dosage, and maternal satisfaction with CSEA were assessed.

Results

Overall, the VAS labor pain score was lowest at the first hour after the anesthesia was given. After 4 h for primiparas and 3 h for multiparas, the VAS score was greater than 3 but the anesthetic drug dosage did not reach the maximum allowed dosage at the same time. The average anesthetic drug dosage was positively correlated with fever, urinary retention, uterine atony, prolonged active phase, prolonged second stage, assisted vaginal delivery, and postpartum hemorrhage. The average anesthetic drug dosage was the highest in women ≤ 20 years old, those with a body mass index (BMI) ≥ 24.9 kg/m2, and those with a primary or secondary education level.

Conclusion

Appropriate age guidance and emphasis on education of labor analgesia, weight management during pregnancy, and real-time anesthetic dosage adjustment during labor based on VAS pain score may have positive effects on the satisfaction of labor analgesia.

Clinical trial number and registry

Clinicaltrials.gov (ChiCTR2100051809).

Keywords

Analgesic effectiveness
Anesthetic drug
Dosage adjustment
Labor analgesia
Labor monitoring
issue-copyright-statement© Japanese Society of Anesthesiologists 2024
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pmcIntroduction

Labor pain can result in negative effects such as dystocia and fetal distress [1]. Labor analgesia can reduce pain and thus the chances of negative effects [2]. Combined spinal-epidural anesthesia (CSEA) can rapidly relieve pain and its analgesic effect was more significant compared with other non-neuraxial analgesic protocols [3, 4], and furthermore, it can reduce the rate of non-medically indicated cesarean deliveries [5, 6]. However, studies have reported that as analgesic time is prolonged the visual analogue scale (VAS) score for pain during labor gradually rises, suggesting that the relief of labor pain becomes insufficient [7, 8]. The specific changes of labor pain and analgesic demand during labor remain unclear because few studies have evaluated time-course changes in effectiveness of analgesia during labor [9].

Jib et al. dynamically assessed pain in adolescents with cancer and provided real-time pain treatment to decrease the intensity of pain [10]. A recent study evaluated the pain scores of women using ibuprofen and oxycodone/acetaminophen for medical abortion pain relief at regular intervals, showing more pain relief and lower use of analgesic agents [11]. These two results suggested that frequent assessment of pain can be used as the basis for pain treatment. Ban et al. adjusted the background drug infusion every hour based on the anesthetic requirement in the previous 1 h for improving maternal analgesia satisfaction in their study of computer-integrated patient-controlled epidural analgesia [12], suggesting that pain assessment and adjustment of analgesia every 1 h is a feasible approach when establishing precise and effective analgesic protocols.

Sufentanil combined with ropivacaine alleviates labor pain significantly, but is associated with dose-dependent side effects such as fever, urinary retention, and uterine atony [13–15]. Studies have shown that drug dose prediction based on influencing factors can improve medication safety [16, 17]. Thus, the effectiveness and safety of analgesics should be always considered together and a fine balance must be searched for to achieve optimal labor analgesia. Studies of this nature, however, have not been performed to examine pain scores, drug dosages, and factors influencing drug dosage for women in labor.

In addition, it has been reported that parity is a factor that influences labor pain and the management standards for primipara and multipara in the new stage of labor are not consistent [18, 19].

To provide reference for the optimization of labor analgesia in the primiparas and multiparas, this study was conducted to assess the time-course of VAS scores during labor within a pre-set CSEA protocol (drug doses included), side effects of anesthetic drug dosage, and maternal satisfaction.

Materials and methods

Study design

This study was a prospective, single-center observational cohort study conducted at the Third Affiliated Hospital of Sun Yat-sen University, an institution with 7,000 deliveries per year and a labor analgesia rate of more than 50%. A total of 3,020 women who delivered from July 2020 to January 2022 were included in the study. They were divided into two groups: primiparas and multiparas. Inclusion criteria included: (1) Singleton pregnancy; (2) Accepted CSEA with PCEA for labor analgesia; (3) No contraindications to the analgesics used or method of administration; (4) Cervical dilation of 2 cm before analgesia was administered; (5) No mental illness. Exclusion criteria included: (1) Twin pregnancies; (2) Breech presentation; (3) Contraindications for vaginal delivery; (4) Combination use of other analgesic methods.

This study was registered at Clinicaltrials.gov, and given the registration number ChiCTR2100051809. The study was approved by the Ethics Committee of the Third Affiliated Hospital of Sun Yat-Sen University (No. [2022] 02–051-01), and all participants provided written informed consent.

Analgesic procedure

According to the relevant literature and guidelines, the program of labor analgesia formulated by the Department of Anesthesiology of this research institution was as follows [3, 13]. With the woman in a lateral decubitus position, 5 μg sufentanil was injected into the subarachnoid space at L2-3, and an epidural catheter attached to the PCEA pump was inserted into the epidural space. Then, a PCEA pump containing a 120 ml solution of 45 µg sufentanil (Yichang Renfu Pharmaceutical Co., Ltd) and 75 mg ropivacaine (AstraZeneca) was started. The pump provided a continuous infusion with a background infusion dose (Dbi) of 6 ml/h, a bolus dosage (Db) of 8 ml, and a lock-out time interval of 15 min. The maximum dosage (Dm) of PCEA pump was 38 ml/h (containing 14.25 µg sufentanil and 23.75 mg ropivacaine). The pump was used until the completion of perineal suturing. Effective analgesia was considered a VAS pain score of ≤ 3. If pain relief was inadequate (VAS score > 3), a supplementary bolus dose of 8 ml was given [1]. The number of supplementary bolus (Ns) of the PCEA pump per hour, total anesthetic drug dosage (Dt) used, and the time of labor analgesia duration (t) were recorded during labor. Based on the 2019 American College of Obstetrics and Gynecology (ACOG) recommendations and drug instructions for the safe dosage of sufentanil and ropivacaine (45 μg/h and 28 mg/h respectively) [3], the safe dosage (Ds) of the PCEA pump was calculated. To ensure the accuracy of data, all the subjects received research education.

Data collection

A VAS pain score (with a VAS-scale printed in a paper) was used to assess labor pain, with 0 = no pain and 10 = pain as bad as it could be [20, 21]. In this study, scores were categorized as 0 = no pain; 1–3 = mild pain; 4–6 = moderate pain; and 7–10 = severe pain [7]. VAS pain scores were recorded before labor analgesia, after labor analgesia that was begun at 10 min, 30 min, and hourly from 1 to 10 h, at full cervical dilatation, and at 1, 2, 3, and 4 h after full cervical dilatation. Because this was an observational study, no additional analgesic dose would be added despite results of real-time assessment indicated that such a dose would be needed. To ensure the accuracy and reliability of data, all the physicians received standardized training.

The primary study variable was the VAS pain score. Data collected include the real-time anesthetic dosage, average anesthetic dosage, the occurrence of side effects including fever, urinary retention, uterine atony, and prolonged fetal heart rate (FHR) deceleration, and adverse labor outcomes including prolonged labor phase, assisted vaginal delivery, postpartum hemorrhage, and neonatal asphyxia.The complications related to CSEA such as epidural hematoma, motor block, accidental dural puncture (ADP) and post-dural puncture headache (PDPH) were also documented. Maternal satisfaction was recorded based on a scale of 1 to 5: 1 = very dissatisfied; 2 = dissatisfied; 3 = fair; 4 = satisfied; and 5 = very satisfied [22].

The real-time dosage of the PCEA pump (Dr) was considered to indicate the real-time anesthetic drug consumption from the PCEA pump during labor per hour. The formula for calculating Dr was: Dr = Dbi + Ns × 8. The average dosage (Da) of PCEA pump was calculated by the following formula: Da = Dt /t.

Statistical analysis

Double-entry data and consistency checks were used (Epidata 3.0) [23]. Data were analyzed using IBM SPSS statistical software and SAS software. Quantitative variables were reported as mean ± standard deviation (SD), and compared by t-test or Wilcoxon rank-sum test. Categorical variables were reported as count and percentage, and compared by the chi-square test or Fisher’s exact test. The reference range of labor anesthesia duration was estimated by the 95% confidence interval (CI). Generalized estimating equation (GEE) analysis was used to analyze the repeated measures (VAS pain score and real-time anesthetic dosage). The correlation between the average anesthetic dosage and side effects or adverse labor outcomes was examined using logistic regression analysis. Spearman’s correlation analysis was used to analyze factors influencing average anesthetic drug dosage. Linear regression analysis was used for assessing factors influencing the average drug dosage after adjustment for multiple factors. The level of significance was set at α = 0.05.

Results

Study participants

A total of 3,020 women participated in this study, among which there were 2,265 primiparas and 755 multiparas (Fig. 1). The clinical information of the 2 groups and P values for assessing group differences are shown in Table 1. The epidural hematoma and motor block did not occur because of the experienced anesthesiologist and adequate preparation. There were 3 and 1 ADP cases in primiparas and multiparas respectively, but no PDPH cases were observed in both groups.Fig. 1 Patient eligibility

Table 1 Comparison of clinical information for primiparas and multiparas

Term	Primiparas (n = 2265)	Multiparas (n = 755)	P value	
Baseline data				
Age (year)	28.7 ± 3.1	32.0 ± 3.8	 < 0.01*	
Gestational week (week)	39.3 ± 1.3	39.3 ± 1.1	NS	
Prenatal BMI (kg/m2)	21.2 ± 3.3	21.6 ± 3.2	NS	
Newborn Weight (kg)	3.0 ± 0.3	3.2 ± 0.3	0.05*	
Education level			NS	
Primary/Secondary	88 (3.8)	36 (4.7)		
High School Education	135 (5.9)	55 (7.2)		
College/University (less than 4 years)	914 (40.3)	293 (38.8)		
College/University (4 years and above)	1128 (49.8)	371 (49.1)		
Clinical data				
The way for induction			NS	
Combined cervical dilation balloons with contraction	245 (10.8)	76 (10.0)		
Cervical dilation balloons	38 (1.7)	11 (1.4)		
Small doses of contractions	207 (9.1)	73 (9.7)		
None	1775 (78.3)	595 (78.7)		
Labor duration (hour)				
Latent phase	7.1 ± 2.7	4.8 ± 2.4	 < 0.01*	
Active phase	3.6 ± 1.4	2.4 ± 1.1	 < 0.01*	
Second stage	1.2 ± 0.8	0.4 ± 0.2	 < 0.01*	
The duration of effective analgesia (hour)	4.2 ± 1.2	3.8 ± 1.1	 < 0.05*	
The duration of labor analgesia (hour)	(8.1–8.6)	(4.0–4.3)	 < 0.05*	
Average anesthetic drug dosage (ml/hour)	10.0 ± 5.0	9.2 ± 5.0	 < 0.01*	
Side effect				
Fever	622 (27.5)	103 (13.6)	 < 0.01*	
Urinary retention	900 (39.7)	204 (27.0)	 < 0.01*	
Uterine atony	994 (43.9)	159 (21.1)	 < 0.01*	
Prolonged FHR deceleration	349 (15.4)	77 (10.2)	 < 0.01*	
Adverse labor outcome				
Prolonged latent phase	211 (9.3)	69 (9.1)	NS	
Prolonged active phase	134 (5.9)	28 (3.7)	0.02*	
Prolonged second stage of labor	78 (3.4)	15 (1.9)	0.04*	
Vaginal assisted birth	156 (6.9)	18 (2.4)	 < 0.01*	
Postpartum hemorrhage	274 (12.0)	66 (8.7)	0.01*	
Complications				
Epidural hematoma	0(0.0)	0(0.0)	NS	
Motor block	0(0.0)	0(0.0)	NS	
Accidental dural puncture	3(0.0)	1(0.0)	NS	
Post-dural puncture headache	0(0.0)	0(0.0)	NS	
Data are presented as mean ± SD or count (%)

BMI body mass index, FHR fetal heart rate

An orifice dilatation of ≥ 6 cm was used as a marker of active stage [24]

NS as non-significant. *Evidence for an association assessed at P value ≤ 0.05

VAS scores and anesthetic drug dosages

As shown in Table 2, the VAS pain scores for primiparas and multiparas were lowest at the first hour after the anesthesia was given. The duration of effective analgesia for primiparas was 4.2 ± 1.2 h, and for multiparas was 3.8 ± 1.1 h, which were significantly shorter than the duration of labor analgesia (Table 1). After 4 h of analgesia for primiparas and 3 h of analgesia for multiparas, the VAS pain scores were > 3 for both groups (Fig. 2A, B).Table 2 Real-time VAS pain score changes during labor with analgesia

Term	Primiparas	Multiparas	
n	VAS	N	VAS	
Before labor analgesia	2265	7.52 ± 1.90	755	7.27 ± 1.90	
After analgesia in the first stage of labor (hour)					
0.17	2265	1.88 ± 1.92	755	2.06 ± 2.01	
0.5	2265	1.15 ± 1.51	755	1.40 ± 1.72	
1	2247	1.07 ± 1.44	712	1.31 ± 1.63	
2	2068	1.74 ± 1.83	536	2.15 ± 2.03	
3	1592	2.73 ± 2.11	339	3.02 ± 2.22	
4	1260	3.63 ± 2.17	192	3.88 ± 2.35	
5	930	4.40 ± 2.10	123	4.57 ± 2.37	
6	692	5.08 ± 2.08	81	5.49 ± 2.06	
7	507	5.55 ± 1.81	40	5.82 ± 2.03	
8	362	6.24 ± 1.98	25	6.72 ± 1.95	
9	258	6.77 ± 2.09	14	7.14 ± 1.99	
10	189	7.21 ± 2.03	11	7.46 ± 1.81	
The second stage of labor (hour)					
0	2265	5.90 ± 2.49	755	6.52 ± 2.41	
1	965	6.92 ± 1.93	93	7.28 ± 2.20	
2	335	7.83 ± 2.23	14	8.00 ± 2.83	
3	89	8.11 ± 2.21	3	10.00 ± 0.00	
4	27	10.00 ± 0.00	-	-	
Data are presented as mean ± SD

Fig. 2 Comparison of analgesia efficacy between primiparas and multiparas at the same moment. The real-time VAS score with the duration of analgesia (A, B) and the real-time anesthetic drug dosage with the duration of analgesia (C, D). Both of the real-time VAS score and the real-time anesthetic drug dosage changed gradually over time (P < 0.05). Dm: the maximum dosage of PCEA pump. Ds: the safe dosage of the PCEA pump

However, after 4 h of analgesia for primiparas and 3 h of analgesia for multiparas, the anesthetic drug dosage was below the maximum dosage (Dm) of the PCEA pump, and below the safe dosage (Ds) of anesthetic drug (Fig. 2A, B). The average anesthetic dosage was higher in primiparas than in multiparas (P < 0.05, Table 1). The GEE analysis revealed that the anesthetic drug dosage increased in tandem with the VAS pain score during the first stage of labor for primiparas and multiparas (both, P < 0.05, Table 3).Table 3 Analysis of real-time VAS pain score and anesthetic drug dosage after analgesia

Term	Primiparas	Multiparas	
Beta	SE	95% CI	P value	Beta	SE	95% CI	P value	
First stage	5.37	0.12	5.13–5.60	 < 0.01	3.23	0.19	2.85–3.61	 < 0.01	
Second stage	0.03	0.02	 – 0.01 to 0.08	0.19	0.02	0.07	0.06–0.08	0.21	

Side effects and adverse labor outcomes

Logistic regression models were developed to determine if the average anesthetic drug dosage was positively associated with the incidence of side effects and adverse labor outcomes. For both primiparas and multiparas, the average drug dosage was positively correlated with fever, urinary retention, uterine atony, prolonged active phase, prolonged second stage, assisted vaginal delivery and postpartum hemorrhage (all, P < 0.05, Fig. 3A–D). The side effects of analgesia and the incidence of adverse labor outcomes were higher in primiparas than in multiparas (both, P < 0.05, Table 1).Fig. 3 Correlation analysis of the average anesthetic dosage with the side effect (A, B) and adverse labor outcomes (C, D)

Univariate and multivariate analysis

Univariate analysis indicated that primipara age, prenatal BMI, newborn weight, and education level, as well as multipara age, prenatal BMI, and education level were all related to the average anesthetic drug dosage (all, P < 0.05, Table 4). Multivariate analysis with adjustment showed that the average anesthetic drug dosage for the 2 groups was influenced by age, prenatal BMI, and education level. In addition, the average anesthetic drug dosage was highest in women ≤ 20 years old, with a BMI ≥ 24.9 kg/m2, and with a primary or secondary education level (Table 4).Table 4 Analysis of factors influencing the average anesthetic dosage

Term	Univariate analysis	Multivariate analysis	
B	95% CI	P value	B	95% CI	P value	
Primiparas							
Age (year)*							
 ≤ 20	– 0.722	– 1.164 to – 0.280	 < 0.01	– 0.642	– 0.966 to – 0.317	 < 0.01	
20–30							
 > 30							
Prenatal BMI (kg/m2)*							
 ≤ 18.5	– 0.704	– 1.055 to – 0.352	 < 0.01	0.158	0.101–0.215	0.03	
18.5–24.9							
 ≥ 24.9							
Newborn Weight (kg)	1.068	0.427–1.709	 < 0.01	0.505	– 0.235 to 1.245	0.18	
Education level*	– 6.448	– 6.679 to – 6.218	 < 0.01	– 6.453	– 6.684 to – 6.222	 < 0.01	
Primary / Secondary							
High School Education							
College/University (less than 4 years)							
College/University (4 years and above)							
Multiparas							
Age (year)*							
 ≤ 20	– 5.439	– 6.080 to – 4.799	 < 0.01	– 2.399	– 2.897 to – 1.900	 < 0.01	
20–30							
 > 30							
Prenatal BMI (kg/m2)*							
 ≤ 18.5	5.589	5.090–6.088	 < 0.01	2.247	1.760–2.734	 < 0.01	
18.5–24.9							
 ≥ 24.9							
Newborn Weight (kg)	−0.465	– 1.382 to 0.453	0.32	–	–	–	
Education level*							
Primary / Secondary	– 3.606	– 3.997 to – 3.216	 < 0.01	– 2.168	– 2.547 to – 1.790	 < 0.01	
High School Education							
College/University (less than 4 years)							
College/University (4 years and above)							
*Evidence for an association assessed at P value ≤ 0.05

Maternal satisfaction

The proportion of multiparas (73.5%) who felt satisfied with labor analgesia was higher than the proportion of primiparas (67.3%). An analysis of the reasons for a satisfaction score ≤ 3 showed a statistical difference for primiparas and multiparas, and poor analgesia was the main cause (χ2 = 17.757). Further analysis showed that compared to multiparas, a smaller proportion of primiparas were unsatisfied with the poor analgesia (55.8%), but had a higher frequency of side effects (13.9%) and prolonged labor (27.1%) (Table 5).Table 5 Satisfaction scores and reasons for unsatisfactory labor analgesia

Term	Primiparas	Multiparas	P value	
Maternal satisfaction			 < 0.01*	
Satisfaction score ≥ 4	1525 (67.3)	555 (73.5)		
Satisfaction score ≤ 3	740 (32.6)	200 (26.4)		
Reasons for unsatisfactory labor analgesia				
Poor analgesia	413 (55.8)	124 (62.0)	 < 0.01*	
Prolonged labor	201 (27.1)	46 (23.0)	0.02*	
Side effect	103 (13.9)	21 (10.5)	 < 0.01*	
Else (such as experience)	23 (3.1)	9 (4.5)	NS	
Data are presented as count (%)

NS as non-significant. *Evidence for an association assessed at P value ≤ 0.05

The maternal satisfaction score ≥ 4 was considered satisfactory for labor analgesia

Discussion

A study by Eran Ashwal in 2020 concluded that the cervical dilation rate during labor analgesia differed between primiparas and multiparas [25]. In the current study, the VAS pain scores were lowest at the first hour after the anesthesia was given, and indicated ineffective analgesia after 4 h for primiparas and 3 h for multiparas. There are a few numbers of reasons for this finding. Firstly, the best analgesic effect may be obtained at these times as a result of the pharmacological action or the method of administration of the anesthetic drug [26]. Secondly, physical exhaustion during labor might lead to a decreased tolerance of labor pain [27], and prolonged opioid usage can result in adaptive changes in μ receptors leading to tolerance and hyperalgesia [28]. The tolerance for labor pain reaches a limit after 4 h of analgesia for primiparas and 3 h of analgesia for multiparas. Thirdly, our results showed that the anesthetic drug dosage increased in tandem with the VAS pain score during the first stage of labor, but the maximum dosage of PCEA pump was not reached after 4 h for primiparas and 3 h for multiparas, prior to which the pump with a pre-set CSEA protocol may provide too much anesthetic drug dosage. After that, the PCEA pump was not fully used, reflecting the limitations of the PCEA pump settings and even the CSEA protocol.

It has been shown that multiparas require a higher median effective concentration of ropivacaine during labor analgesia due to psychogenic pain from previous labor pain experiences [29]. This is consistent with the satisfaction survey of this study which showed that compared to primiparas, more multiparas experienced poor labor analgesia. So, primiparas and multiparas may require different management and awareness of self-management should be given more attention. In our study, we also found that insufficient dosage was one of the factors leading to unsatisfactory labor analgesia for both primiparas and multiparas. Therefore, clinicians need to adjust the background infusion dose, the bolus dosage, or the lock-out time of PCEA pump timely under the safe dosage of sufentanil and ropivacaine (45 μg/h and 28 mg/h respectively [3]) and educate women that the drug dosage may be increased according to the real-time VAS pain score in order to provide more prolonged relief of pain after 4 h of analgesia for primiparas and 3 h of analgesia for multiparas [30, 31].

The incidence of fever is associated with the dose of anesthetic drugs, and fever associated with ropivacaine is due to the release of inflammatory factors caused by ropivacaine, while the use of sufentanil may result in impairment of the central thermoregulatory response [32, 33]. Armstrong et al. proposed that opioid-induced urinary retention is related to dosage, and may be the result of detrusor muscle dysfunction or because the drug impedes the afferent and efferent mechanisms of the voiding reflex [34]. The aforementioned studies help to explain our observation. It also showed that the average anesthetic drug dosage was associated with uterine atony, prolonged active phase, prolonged second stage, assisted vaginal delivery and postpartum hemorrhage. These findings could be related to a decrease in the frequency and intensity of uterine contractions, because the nerves innervating the uterus are inhibited by CSEA resulting in uterine atony. And uterine atony and assisted vaginal delivery are known as risk factors for postpartum hemorrhage [35–38]. Primiparas may have a higher average anesthetic drug dosage due to their longer duration of labor analgesia, and this may be why a higher proportion of primiparas were dissatisfied due to side effects and prolonged labor.

It has been shown that an increased BMI is linked to increased technical difficulties and failure of epidural analgesia for labor, resulting in insufficient analgesia [39]. Junge et al. reported a strong correlation between severe fear and labor pain. Younger women, who may feel more fear of childbirth due to a lack of education have a higher demand for analgesic drugs [40]. On the other hand, women with higher education levels have a higher awareness of analgesia and get more effective pain relief [31]. As revealed in this study, the average anesthetic drug dosage was the highest in the groups ≤ 20 years old, BMI ≥ 24.9 kg/m2, and those with a primary or secondary education level. The findings of our study also demonstrated that there was still potential for ropivacaine and sufentanil dosage adjustments of CSEA for labor analgesia. The parturients received relevant education before labor through various means, including network courses offered by our hospital, to alleviate anxiety and provide information on the use of anesthetics and their side effects. However, their awareness of the current CSEA protocol remained limited. As for the reasons of unsatisfactory labor analgesia, insufficient analgesia was the main cause, followed by side effects and prolonged labor, among which the primiparas and multiparas were different. So individualized labor analgesia programs based on real-time VAS pain score and parity could be establish (ex. multiparas want more analgesics, primiparas are more concerned about the side effects of labor analgesia, etc.). Furthermore, clinicians should strengthen weight management during pregnancy and educate patients regarding labor analgesia awareness to reduce the use of anesthetic drugs, in order to achieve the balance between sufficient analgesic and side effects of administered drugs during the whole course of labor.

There may be some possible limitations in this study. First, the selection of 1-h intervals for VAS pain scores during labor analgesia had the time constraint, which might be shortened to make the assessment more specific. Second, a future study should be conducted in multicenter study to validate the findings in our one-institution-based study. Third, only one CSEA protocol was researched in this study. And fourth, there were also possible confounding factors that have not been studied, including environmental factors, family factors and so on.

Conclusion

Clinician should establish individualized labor analgesia programs based on real-time VAS pain score and parity. At the same time, education of labor analgesia should be strengthened to enhance the effectiveness of labor analgesia, reduce side effects, and improve maternal satisfaction.

Acknowledgements

The authors thank all the parturient who participated in this study.

Author contributions

Shuzhen Wu: project development, data collection, data analysis, interpretation of data, manuscript writing, approval of the final version. Yaxin Lu: data analysis, interpretation of data, revision of the manuscript. Zijing Zhang: data collection. Linjia Zhong: data collection. Hongfei Dai: data collection. Changping Fang: data collection, revision of the manuscript. Minli Huang: data collection. Zifeng Liu: data analysis, interpretation of data. Lingling Wu: project development, interpretation of data, manuscript writing, approval of the final version.

Funding

The authors have no sources of funding to declare for this manuscript.

Data availability

The data that support the findings of this study are available on request from the corresponding author, [LW], upon reasonable request.

Declarations

Conflict of interest

The authors declare no conflicts of interest.

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References

1. Rooks JP Labor pain management other than neuraxial: what do we know and where do we go next? Birth 2012 39 4 318 322 10.1111/birt.12009 23281953
Rooks JP. Labor pain management other than neuraxial: what do we know and where do we go next? Birth. 2012;39(4):318–22.23281953
2. Yin H Tong X Huang H Dural puncture epidural versus conventional epidural analgesia for labor: a systematic review and meta-analysis of randomized controlled studies J Anesth 2022 36 3 413 427 10.1007/s00540-022-03061-8 35445869
Yin H, Tong X, Huang H. Dural puncture epidural versus conventional epidural analgesia for labor: a systematic review and meta-analysis of randomized controlled studies. J Anesth. 2022;36(3):413–27.35445869
3. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 209: Obstetric Analgesia and Anesthesia. Obstet Gynecol. 2019;133(3): e208-e225.
4. Lam KK Leung MKM Irwin MG Labour analgesia: update and literature review Hong Kong Med J 2020 26 5 413 420 32943586
Lam KK, Leung MKM, Irwin MG. Labour analgesia: update and literature review. Hong Kong Med J. 2020;26(5):413–20.32943586
5. Bonnet MP Prunet C Baillard C Kpéa L Blondel B Le Ray C Anesthetic and obstetrical factors associated with the effectiveness of epidural analgesia for labor pain relief: an observational population-based study Reg Anesth Pain Med 2017 42 1 109 116 10.1097/AAP.0000000000000517 27831958
Bonnet MP, Prunet C, Baillard C, Kpéa L, Blondel B, Le Ray C. Anesthetic and obstetrical factors associated with the effectiveness of epidural analgesia for labor pain relief: an observational population-based study. Reg Anesth Pain Med. 2017;42(1):109–16.27831958
6. Wang Q Zheng SX Ni YF Lu YY Zhang B Lian QQ Hu MP The effect of labor epidural analgesia on maternal-fetal outcomes: a retrospective cohort study Arch Gynecol Obstet 2018 298 1 89 96 10.1007/s00404-018-4777-6 29777348
Wang Q, Zheng SX, Ni YF, Lu YY, Zhang B, Lian QQ, Hu MP. The effect of labor epidural analgesia on maternal-fetal outcomes: a retrospective cohort study. Arch Gynecol Obstet. 2018;298(1):89–96.29777348
7. Sun X Zhou Q Zhou M Cao R Chen Z Tang S Huang S The effect of epidural nalbuphine combined with ropivacaine on epidural analgesia during labor: a multicenter, randomized, double-blind, controlled study Clin J Pain 2021 37 6 437 442 10.1097/AJP.0000000000000928 33758132
Sun X, Zhou Q, Zhou M, Cao R, Chen Z, Tang S, Huang S. The effect of epidural nalbuphine combined with ropivacaine on epidural analgesia during labor: a multicenter, randomized, double-blind, controlled study. Clin J Pain. 2021;37(6):437–42.33758132
8. Song Y Du W Zhou S Zhou Y Yu Y Xu Z Liu Z Effect of dural puncture epidural technique combined with programmed intermittent epidural bolus on labor analgesia onset and maintenance: a randomized controlled trial AnesthAnalg 2021 132 4 971 978
Song Y, Du W, Zhou S, Zhou Y, Yu Y, Xu Z, Liu Z. Effect of dural puncture epidural technique combined with programmed intermittent epidural bolus on labor analgesia onset and maintenance: a randomized controlled trial. AnesthAnalg. 2021;132(4):971–8.
9. Mao L Zhang X Zhu J Analgesic effects, birth process, and prognosis of pregnant women in normal labor by epidural analgesia using sufentanil in combination with ropivacaine: a retrospective cohort study ComputIntellNeurosci 2022 2022 1228006
Mao L, Zhang X, Zhu J. Analgesic effects, birth process, and prognosis of pregnant women in normal labor by epidural analgesia using sufentanil in combination with ropivacaine: a retrospective cohort study. ComputIntellNeurosci. 2022;2022:1228006.
10. Jibb L Nathan PC Breakey V Fernandez C Johnston D Lewis V McKillop S Patel S Sabapathy C Strahlendorf C Victor JC Moretti ME Nguyen C Hundert A Cassiani C El-KhechenRichandi G Insull H Hamilton R Fang G Kuczynski S Stinson J Pain Squad+ smartphone app to support real-time pain treatment for adolescents with cancer: protocol for a randomised controlled trial BMJ Open 2020 10 3 e037251 10.1136/bmjopen-2020-037251 32184315
Jibb L, Nathan PC, Breakey V, Fernandez C, Johnston D, Lewis V, McKillop S, Patel S, Sabapathy C, Strahlendorf C, Victor JC, Moretti ME, Nguyen C, Hundert A, Cassiani C, El-KhechenRichandi G, Insull H, Hamilton R, Fang G, Kuczynski S, Stinson J. Pain Squad+ smartphone app to support real-time pain treatment for adolescents with cancer: protocol for a randomised controlled trial. BMJ Open. 2020;10(3): e037251.32184315
11. Friedlander EB Raidoo S Soon R Salcedo J Davis J Tschann M Fontanilla T Horiuchi W Kaneshiro B The experience of pain in real-time during medication abortion Contraception 2022 110 71 75 10.1016/j.contraception.2022.03.003 35283083
Friedlander EB, Raidoo S, Soon R, Salcedo J, Davis J, Tschann M, Fontanilla T, Horiuchi W, Kaneshiro B. The experience of pain in real-time during medication abortion. Contraception. 2022;110:71–5.35283083
12. Sng BL Woo D Leong WL Wang H Assam PN Sia AT Comparison of computer-integrated patient-controlled epidural analgesia with no initial basal infusion versus moderate basal infusion for labor and delivery: a randomized controlled trial J Anaesthesiol Clin Pharmacol 2014 30 4 496 501 10.4103/0970-9185.142842 25425774
Sng BL, Woo D, Leong WL, Wang H, Assam PN, Sia AT. Comparison of computer-integrated patient-controlled epidural analgesia with no initial basal infusion versus moderate basal infusion for labor and delivery: a randomized controlled trial. J Anaesthesiol Clin Pharmacol. 2014;30(4):496–501.25425774
13. Wang Y Xu M Comparison of ropivacaine combined with sufentanil for epidural anesthesia and spinal-epidural anesthesia in labor analgesia BMC Anesthesiol 2020 20 1 1 10.1186/s12871-019-0855-y 31898488
Wang Y, Xu M. Comparison of ropivacaine combined with sufentanil for epidural anesthesia and spinal-epidural anesthesia in labor analgesia. BMC Anesthesiol. 2020;20(1):1.31898488
14. Anim-Somuah M, Smyth RM, Cyna AM, Cuthbert A. Epidural versus non-epidural or no analgesia for pain management in labour. Cochrane Database Syst Rev. 2018;5(5):CD000331.
15. Edwards IR Aronson JK Adverse drug reactions: definitions, diagnosis, and management Lancet 2000 356 9237 1255 1259 10.1016/S0140-6736(00)02799-9 11072960
Edwards IR, Aronson JK. Adverse drug reactions: definitions, diagnosis, and management. Lancet. 2000;356(9237):1255–9.11072960
16. Salinas AS Lorenzo-Romero J Segura M Calero MR Hernández-Millán I Martínez-Martín M Virseda JA Factors determining analgesic and sedative drug requirements during extracorporeal shock wave lithotripsy Urol Int 1999 63 2 92 101 10.1159/000030425 10592496
Salinas AS, Lorenzo-Romero J, Segura M, Calero MR, Hernández-Millán I, Martínez-Martín M, Virseda JA. Factors determining analgesic and sedative drug requirements during extracorporeal shock wave lithotripsy. Urol Int. 1999;63(2):92–101.10592496
17. Hashimoto M Aogaki K Numata C Moriwaki K Matsuda Y Ishii R Tanaka I Okamoto Y Factors influencing the prescribed dose of opioid analgesics in cancer patients J Opioid Manag 2020 16 4 247 252 10.5055/jom.2020.0578 32885832
Hashimoto M, Aogaki K, Numata C, Moriwaki K, Matsuda Y, Ishii R, Tanaka I, Okamoto Y. Factors influencing the prescribed dose of opioid analgesics in cancer patients. J Opioid Manag. 2020;16(4):247–52.32885832
18. Westergren A Edin K Lindkvist M Christianson M Exploring the medicalisation of childbirth through women’s preferences for and use of pain relief Women Birth 2021 34 2 e118 e127 10.1016/j.wombi.2020.02.009 32094035
Westergren A, Edin K, Lindkvist M, Christianson M. Exploring the medicalisation of childbirth through women’s preferences for and use of pain relief. Women Birth. 2021;34(2):e118–27.32094035
19. Expert consensus on new labor standards and management [J]. Chinese J Obstet Gynecol 2014:49(07):486.
20. Thorburn PT, Monteiro R, Chakladar A, Cochrane A, Roberts J. South East Anaesthetic Research Chain (SEARCH), Mark Harper C. Maternal temperature in emergency caesarean section (MATES): an observational multicentre study. Int J ObstetAnesth. 2021;46:102963.
21. Thong ISK Jensen MP Miró J Tan G The validity of pain intensity measures: what do the NRS, VAS, VRS, and FPS-R measure? Scand J Pain 2018 18 1 99 107 10.1515/sjpain-2018-0012 29794282
Thong ISK, Jensen MP, Miró J, Tan G. The validity of pain intensity measures: what do the NRS, VAS, VRS, and FPS-R measure? Scand J Pain. 2018;18(1):99–107.29794282
22. Wang Fen, LI Yan, Chen Feng-Ren, et al. Effect of maternal satisfaction with labor analgesia on postpartum depression. Modern Preventive Medicine, 2020;47(06):1028–1031+1051.
23. Yue-song PAN Data management and quality control for clinical research Med J Pumch 2018 9 5 458 462
Yue-song PAN. Data management and quality control for clinical research. Med J Pumch. 2018;9(5):458–62.
24. Zhang J, Landy HJ, Ware Branch D, Burkman R, Haberman S, Gregory KD, Hatjis CG, Ramirez MM, Bailit JL, Gonzalez-Quintero VH, Hibbard JU, Hoffman MK, Kominiarek M, Learman LA, Van Veldhuisen P, Troendle J, Reddy UM. Consortium on Safe Labor. Contemporary patterns of spontaneous labor with normal neonatal outcomes. Obstet Gynecol. 2010;116(6):1281–1287.
25. Ashwal E Livne MY Benichou JIC Unger R Hiersch L Aviram A Mani A Yogev Y Contemporary patterns of labor in nulliparous and multiparous women Am J Obstet Gynecol 2020 222 3 267.e1 267.e9 10.1016/j.ajog.2019.09.035 31574290
Ashwal E, Livne MY, Benichou JIC, Unger R, Hiersch L, Aviram A, Mani A, Yogev Y. Contemporary patterns of labor in nulliparous and multiparous women. Am J Obstet Gynecol. 2020;222(3):267.e1-267.e9.31574290
26. Congedo E Sgreccia M De Cosmo G New drugs for epidural analgesia Curr Drug Targets 2009 10 8 696 706 10.2174/138945009788982441 19702518
Congedo E, Sgreccia M, De Cosmo G. New drugs for epidural analgesia. Curr Drug Targets. 2009;10(8):696–706.19702518
27. Siyoum M Mekonnen S Labor pain control and associated factors among women who gave birth at Leku primary hospital, southern Ethiopia BMC Res Notes 2019 12 1 619 10.1186/s13104-019-4645-x 31547839
Siyoum M, Mekonnen S. Labor pain control and associated factors among women who gave birth at Leku primary hospital, southern Ethiopia. BMC Res Notes. 2019;12(1):619.31547839
28. Colvin LA Bull F Hales TG Perioperative opioid analgesia-when is enough too much? A review of opioid-induced tolerance and hyperalgesia Lancet 2019 393 10180 1558 1568 10.1016/S0140-6736(19)30430-1 30983591
Colvin LA, Bull F, Hales TG. Perioperative opioid analgesia-when is enough too much? A review of opioid-induced tolerance and hyperalgesia. Lancet. 2019;393(10180):1558–68.30983591
29. Peng Q Yang Z Zhang W Wu X Comparison of median effective concentration of ropivacaine in multiparas or primiparas during epidural labor analgesia: STROBE compliant Medicine (Baltimore) 2020 99 1 e18673 10.1097/MD.0000000000018673 31895835
Peng Q, Yang Z, Zhang W, Wu X. Comparison of median effective concentration of ropivacaine in multiparas or primiparas during epidural labor analgesia: STROBE compliant. Medicine (Baltimore). 2020;99(1): e18673.31895835
30. Gido R Yadeta TA Tura AK Utilization of obstetric analgesia for labor pain management and associated factors among obstetric care providers in public hospitals of addis ababa, ethiopia: a cross-sectional study ObstetGynecol Int 2021 2021 9973001
Gido R, Yadeta TA, Tura AK. Utilization of obstetric analgesia for labor pain management and associated factors among obstetric care providers in public hospitals of addis ababa, ethiopia: a cross-sectional study. ObstetGynecol Int. 2021;2021:9973001.
31. Ali Alahmari SS, ALmetrek M, Alzillaee AY, Hassan WJ, Ali Alamry SM. Knowledge, attitude, and practice of childbearing women toward epidural anesthesia during normal vaginal delivery in Alsanayeah Primary Health Care in Khamis Mushait. J Family Med Prim Care. 2020;9(1):99–104.
32. Zhou X Li J Deng S Xu Z Liu Z Ropivacaine at different concentrations on intrapartum fever, IL-6 and TNF-α in parturient with epidural labor analgesia Exp Ther Med 2019 17 3 1631 1636 30783430
Zhou X, Li J, Deng S, Xu Z, Liu Z. Ropivacaine at different concentrations on intrapartum fever, IL-6 and TNF-α in parturient with epidural labor analgesia. Exp Ther Med. 2019;17(3):1631–6.30783430
33. Tian F Wang K Hu J Xie Y Sun S Zou Z Huang S Continuous spinal anesthesia with sufentanil in labor analgesia can induce maternal febrile responses in puerperas Int J Clin Exp Med 2013 6 5 334 341 23724151
Tian F, Wang K, Hu J, Xie Y, Sun S, Zou Z, Huang S. Continuous spinal anesthesia with sufentanil in labor analgesia can induce maternal febrile responses in puerperas. Int J Clin Exp Med. 2013;6(5):334–41.23724151
34. Armstrong S Fernando R Side effects and efficacy of neuraxial opioids in pregnant patients at delivery: a comprehensive review Drug Saf 2016 39 5 381 399 10.1007/s40264-015-0386-5 26832926
Armstrong S, Fernando R. Side effects and efficacy of neuraxial opioids in pregnant patients at delivery: a comprehensive review. Drug Saf. 2016;39(5):381–99.26832926
35. Grant EN Tao W Craig M McIntire D Leveno K Neuraxial analgesia effects on labour progression: facts, fallacies, uncertainties and the future BJOG 2015 122 3 288 293 10.1111/1471-0528.12966 25088476
Grant EN, Tao W, Craig M, McIntire D, Leveno K. Neuraxial analgesia effects on labour progression: facts, fallacies, uncertainties and the future. BJOG. 2015;122(3):288–93.25088476
36. Sultan P Murphy C Halpern S Carvalho B The effect of low concentrations versus high concentrations of local anesthetics for labour analgesia on obstetric and anesthetic outcomes: a meta-analysis Can J Anaesth 2013 60 9 840 854 10.1007/s12630-013-9981-z 23925722
Sultan P, Murphy C, Halpern S, Carvalho B. The effect of low concentrations versus high concentrations of local anesthetics for labour analgesia on obstetric and anesthetic outcomes: a meta-analysis. Can J Anaesth. 2013;60(9):840–54.23925722
37. Hawker L Weeks A Postpartum haemorrhage (PPH) rates in randomized trials of PPH prophylactic interventions and the effect of underlying participant PPH risk: a meta-analysis BMC Pregnancy Childbirth 2020 20 1 107 10.1186/s12884-020-2719-3 32054453
Hawker L, Weeks A. Postpartum haemorrhage (PPH) rates in randomized trials of PPH prophylactic interventions and the effect of underlying participant PPH risk: a meta-analysis. BMC Pregnancy Childbirth. 2020;20(1):107.32054453
38. Xiao J Yi W Wu L Effects of electroacupuncture on reducing labor pain and complications in the labor analgesia process of combined spinal-epidural analgesia with patient-controlled epidural analgesia Arch Gynecol Obstet 2019 299 1 123 128 10.1007/s00404-018-4955-6 30426192
Xiao J, Yi W, Wu L. Effects of electroacupuncture on reducing labor pain and complications in the labor analgesia process of combined spinal-epidural analgesia with patient-controlled epidural analgesia. Arch Gynecol Obstet. 2019;299(1):123–8.30426192
39. Vernon TJ Vogel TM Dalby PL Mandell G Lim G Ultrasound-assisted epidural labor analgesia for landmark identification in morbidly obese pregnant women: a preliminary investigation J Clin Anesth 2020 59 53 54 10.1016/j.jclinane.2019.05.023 31226533
Vernon TJ, Vogel TM, Dalby PL, Mandell G, Lim G. Ultrasound-assisted epidural labor analgesia for landmark identification in morbidly obese pregnant women: a preliminary investigation. J Clin Anesth. 2020;59:53–4.31226533
40. Junge C von Soest T Weidner K Seidler A Eberhard-Gran M Garthus-Niegel S Labor pain in women with and without severe fear of childbirth: a population-based, longitudinal study Birth 2018 45 4 469 477 10.1111/birt.12349 29630751
Junge C, von Soest T, Weidner K, Seidler A, Eberhard-Gran M, Garthus-Niegel S. Labor pain in women with and without severe fear of childbirth: a population-based, longitudinal study. Birth. 2018;45(4):469–77.29630751
